The long-term goal of this research is to develop ultra-sensitive magnetic resonance imaging (MRI) probes that can provide cancer-specific detection of lung tumors by MRI. MRI is a clinical imaging technique that has broad applications in non-invasive diagnosis and post-therapy assessment for cancer. Although Gd-DTPA (Magnevist.) and other small molecular weight agents work well for dynamic contrast enhancement MRI applications, these agents are not very sensitive (lower limit of detection is ~10-4 M) and therefore cannot be used for detecting specific biological markers in vivo. In this application, we will investigate the use of superparamagnetic polymeric micelles (SPPM) that are loaded with a cluster of magnetite nanoparticles for molecular imaging of lung cancer. This platform demonstrated ~20 pM sensitivity of detection by MRI that will be essential for diagnosing lung cancers. A novel class of lung cancer-targeting peptides (LCPs) identified from phage screening will be functionalized on the surface of SPPM to target lung cancer cells. The isolated peptides demonstrated remarkable binding affinities (

Public Health Relevance

A combination of novel MRI imaging method and ultra-sensitive molecular probes will be developed to provide cell-specific characterization of lung tumors. This knowledge can facilitate timely intervention of lung cancer to achieve personalized medicine.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA129011-03
Application #
7809639
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Tandon, Pushpa
Project Start
2008-07-09
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
3
Fiscal Year
2010
Total Cost
$325,775
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Pharmacology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Luo, Min; Wang, Hua; Wang, Zhaohui et al. (2017) A STING-activating nanovaccine for cancer immunotherapy. Nat Nanotechnol 12:648-654
Wang, Chensu; Wang, Yiguang; Li, Yang et al. (2015) A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles. Nat Commun 6:8524
Wang, Yiguang; Zhou, Kejin; Huang, Gang et al. (2014) A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals. Nat Mater 13:204-12
Huang, Xiaonan; Huang, Gang; Zhang, Shanrong et al. (2013) Multi-chromatic pH-activatable 19F-MRI nanoprobes with binary ON/OFF pH transitions and chemical-shift barcodes. Angew Chem Int Ed Engl 52:8074-8
Zhang, Shanrong; Zhou, Kejin; Huang, Gang et al. (2013) A novel class of polymeric pH-responsive MRI CEST agents. Chem Commun (Camb) 49:6418-20
Huang, Gang; Chen, Huabing; Dong, Ying et al. (2013) Superparamagnetic iron oxide nanoparticles: amplifying ROS stress to improve anticancer drug efficacy. Theranostics 3:116-26
Togao, Osamu; Kessinger, Chase W; Huang, Gang et al. (2013) Characterization of lung cancer by amide proton transfer (APT) imaging: an in-vivo study in an orthotopic mouse model. PLoS One 8:e77019
Yu, Haijun; Zou, Yonglong; Wang, Yiguang et al. (2011) Overcoming endosomal barrier by amphotericin B-loaded dual pH-responsive PDMA-b-PDPA micelleplexes for siRNA delivery. ACS Nano 5:9246-55
Ding, Huiying; Mora, Ruben; Gao, Jinming et al. (2011) Characterization and optimization of mTHPP nanoparticles for photodynamic therapy of head and neck cancer. Otolaryngol Head Neck Surg 145:612-7
Doi, Shigehiro; Zou, Yonglong; Togao, Osamu et al. (2011) Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem 286:8655-65

Showing the most recent 10 out of 20 publications